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It appears from everybody's comments it may be a good idea to revisit my initial assumptions and load calculations with HVAC Calc.

Additional background:
The house is a one story rancher with a 250 sqft loft. The loft has a cathedral ceiling with skylights and I plan to possibly add a split system just for the loft at a later time. My HVAC-Calc calculation incorporates the entire house including loft and app. 1000 sqft unfinished basement (total 5,375 sqft). I am only considering the AC design conditions because I am also using radiant heating throughout the house so my duct work should be designed for the AC load, not heating. All of the duct work and the inside units will be in conditioned space (I have a big house so no need to run the duct work in the attic). I entered 100 degees outside and 73 degrees inside after discussing this with my wife (who likes a very cool house) and several HVAC contractors in the area who uses 100 degrees with manual j.

Did you add people load in every room? Did you add for kitchen load. Did you realistically account for infiltration? Did you even consider that insulation never performs to rating?
Did you know that a 4 ton AC does not deliver 4 tons at every design load?
Lots of luck distributing 1600cfm to 5400 sf of two level.
I would not consider anything less than two 3 tons.

That looks like just the sensable heat gain.
If so, the sensable heat gain is higher than any 5 ton system from any manufacturer could ever possibly produce at the design conditions you used...

IMO, a house that size needs 2 systems, possibly with some additional zoning, If you really want it to be comforterable in all parts of the house all the time.

If you absolutely insist on sticking with the 100/73 design conditions, I would recommend you look into a whole house dehumidification system. Your HVAC system is going to be somewhat oversized and will not run nearly enough in more normal conditions to control the humidity in your home.

It has been my experience that virtually everyone I encounter that likes to keep it very cool in thier home has a humidity control problem that causes thier home to be uncomforterable at more normal indoor temperatures...

Sizing the system for conditions that occure <1% of the time is a bad idea, the system may not perform well for the other >99% of the time.

House layout

Downtown,
I designed my own house. It has two levels the lower level has a walk-out. The ductwork and equipment were designed to be in the "conditioned space". That saves a lot of lost capacity but it won't overcome your need for excellent distribution. My cathedral ceiling is 33 high from the open below lower level. Your going to need a very well planned and thought out duct system and probably two separate A/C units, one for each end of the house.
Mark's idea of two units with zoning makes sense to me. Yes, rethink your original ideas.
Phil

Originally posted by mark beiser That looks like just the sensable heat gain.
If so, the sensable heat gain is higher than any 5 ton system from any manufacturer could ever possibly produce at the design conditions you used...

If you absolutely insist on sticking with the 100/73 design conditions, I would recommend you look into a whole house dehumidification system. Your HVAC system is going to be somewhat oversized and will not run nearly enough in more normal conditions to control the humidity in your home.

It has been my experience that virtually everyone I encounter that likes to keep it very cool in thier home has a humidity control problem that causes thier home to be uncomforterable at more normal indoor temperatures...

Sizing the system for conditions that occure <1% of the time is a bad idea, the system may not perform well for the other >99% of the time.

Right on, Mark. The most hours of summer weather are the evening hours + rainy cool weather. During these conditions, sensible and latent loads are equal. This can be verified by analizing typical weather date from DOE. Plug 80^F, 80%RH into Manual J. We depend on over-drying of the home during high a/c loads to carry us through high latent. This is ok for evening hours and one rainy day. During a wet week or two, there is no way to remove enough moister to maintain <50%RH without reheat or supplemental dehumidification.
The solution to the problem is to size the a/c for the your desire preformance at high load condition. This provides temperature and <50%Rh during high loads. I prefer supplement high eff. whole house dehumidification to provide humidity control for the more common low sensible load conditions. This allows not operating the a/c when the home is unoccupied for extended times. Also you can have a more comfortable and efficient 78^F, 45%RH which decreases overall operating cost. Fresh air ventilation/filtering is another advantage of the whole house system. Great posts. Dehu TB

Ok, are you saying I need to model the temperature values for typical or worst case conditions? I understand my insulation, infiltration values will not be as planned so should I fudge the numbers or enter a safety factor for a slight over design?

Additional background:
(p.s. I wish I could pay everybody here for this great advice)

The loft and cathedral is in the middle section of the house above the family room and adjacent to the entry and the kitchen in an open design (i.e no doors). I do not think I can split the the house horizontally in half for two separate systems. Instead I think it makes sense to add either a separate unit for the basement and/or loft possible a split system for the loft. The house is completely framed and under roof. I am adding the radiant in the next two weeks.

To make matters more complicated (sorry but this is my once in a lifetime house!) I plan to use geothermal for both heating and AC. Water to water for radiant heating and water to air for AC. I am very close (65ft) to a large lake and I have 13GPM pump capacity well (up to 25gpm flow) for either an open or closed loop system. I will need a six ton unit for water to water heating. ECONAR offers an affordable dual mode 6 ton for both water to water heating and water to air cooling.

Design conditions

Surely you noticed that in Richmond VA, HVAC-CALC recommends an outdoor design temperature of 92F. Also 111 grains moisture. This is not too very different from Houston TX conditions, a little milder but not much. In my own house at 50% indoor RH I feel downright chilly at 76-77F, comfortable at 77-78F. Are you sure you want to design for 73F indoors?

I can sympathize with the desire to boost the outdoor design temp to something you see a few times per year. I keep worrying myself about a repeat of 1980 weather, an exceptionally hot summer. Tried 99F for my own calc and it made no more than a half ton difference. The pros say you won't need to stretch design conditions, but lots of them do for their own reasons. I cannot say what the right answer is but my own worry zone pushes me to choose 99F myself, on the grounds there ARE a few entire years where the weather is well above average. Which leads me to want a 2-stage system to better hedge my bets.

Safety factor

Don Sleeth, the designer of HVAC Calc, notes several times in his directions that there is NO safety factor built into the calculations. He recommends an additional safety factor of 20% to 25% be applied when using the calculations from his program. He also emphasizes understanding the need to balance calculations for sensible and latent heat gain, almost an "Art" in itself taking into account the number of different coils, TXVs, operating cfms, etc. and other equipment.
Phil

Look at your house again. Walk around it. Try to imagine a way to split the building. I suggest (1) 3 ton 2 stg system and (1) 2 ton 2 stg system. Look at putting the 3 ton to cool the cathedral areas. Get some registers up hi in that area. Find a contractor you are comfortable with and have them walk through the layout with you.